Migraine preventive drug-induced weight gain may be mediated by effects on hypothalamic peptides: the results of a pilot study.

AIMS: This study was aimed to verify changes in the levels of hypothalamic neuropeptides in migraineurs under preventive treatment with amitryptiline and flunarizine. Thirty-nine migraine patients with a body mass index <25 kg/m(2) and without endocrinological or metabolic diseases were assigned to two treatment groups, one receiving amitryptiline, the other flunarizine, for 3 months. Orexin-A, orexin-B and neuropeptide-Y plasma levels were measured at the basal time, at the 1st, 2nd and 3rd months of preventive treatment. RESULTS: A statistically significant reduction in plasma orexin-A and orexin-B levels emerged in both groups. Conversely, plasma neuropeptide-Y levels were markedly increased, with the highest levels at the 2nd and 3rd months, in both patient groups. Orexin-A levels were also negatively correlated to weight gain in both groups during the treatment period. CONCLUSIONS: These results suggest that changes in the levels of hypothalamic orexinergic peptides may contribute to body weight increase occurring in migraineurs during amitryptiline or flunarizine prophylactic treatment.

Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels.

BACKGROUND: Chronic migraine (CM) and medication-overuse headaches (MOH) are well-recognized disabling conditions affecting a significant portion of the headache population attending centers specialized in treating headaches. A dysfunctioning of the serotonergic system has been demonstrated in MOH and CM patients. Here we report on our assessment of the dysfunctioning of the endocannabinoid system as a potential underlying factor in pathogenic mechanisms involved in CM and MOH. METHOD: To test the hypothesis of an impairment in the endocannabinoid system in patients with MOH and CM and to assess its relationship with any disruption of the serotonergic system, we determined the levels of the two main endogenous cannabinoids, anandamide (AEA) and 2-acylglycerol (2-AG), in platelets of 20 CM patients, 20 MOH patients and 20 control subjects and also measured the platelet serotonin levels in the same patients. RESULTS: We found that 2-AG and AEA levels were significantly lower in MOH patients and CM patients than in the control subjects, without significant differences between the two patient groups. Serotonin levels were also strongly reduced in the two patient groups and were correlated with 2-AG levels, with higher values for MOH patients. CONCLUSION: These data support the potential involvement of a dysfunctioning of the endocannabinoid and serotonergic systems in the pathology of CM and MOH. These systems appear to be mutually related and able to contribute to the chronification of both CM and MOH.